Reproductive windows, genetic loci, and breast cancer risk

Abstract

Purpose The reproductive windows between age at menarche and first childbirth (standardized AFB) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk. Methods We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews and DNA samples were collected on a sub-sample (N=1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated and P-values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models. Results For standardized AFB, the OR was 1.52 (CI:1.36-1.71) comparing the highest to lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P=0.04 and P=0.02, respectively). For reproductive lifespan, the OR comparing the highest and lowest quintiles was 1.62 (CI:1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P>0.05). All results were similar regardless of ductal versus lobular breast cancer subtype. Conclusions Our results suggest reproductive windows are associated with breast cancer risk, and that associations may vary by genetic variants.

Is age of menarche directly related to vitamin D levels?

“…Early menarche has been linked to obesity (Prentice & Viner, 2013; Sumi et al, 2018; van Lenthe et al, 1996), type 2 diabetes (Elks et al, 2013; He et al, 2010; Sumi et al, 2018; Zhang, Li, et al, 2019a), gestational diabetes (Chen et al, 2016; Li et al, 2017; Petry et al, 2018; Schoenaker & Mishra, 2017), cardiovascular diseases (X. Chen et al, 2018; Lakshman et al, 2009), endometrial (Dossus et al, 2010), and breast cancers (Ambrosone et al, 2015; Fuhrman et al, 2021; Hsieh et al, 1990), and overall mortality (X. Chen et al, 2018; Lakshman et al, 2009; Zhang, Liu, et al, 2019b). Some of these associations are supported by findings at molecular level at different stages of the disease pathways (Ambrosone et al, 2015; Daraei et al, 2019; Day et al, 2017; Mansoori et al, 2018; Warren Andersen et al, 2014). Furthermore, early age of menarche creates a gap between biological and social maturity, with being biologically adult but socially and legally minor (Gluckman & Hanson, 2006) possibly leading to early sexual debut, potential sexual abuse, alcohol use, and psychosocial difficulties (Deardorff et al, 2005; Golub et al, 2008).…”

“…Chen et al, 2018;Lakshman et al, 2009;Zhang, Liu, et al, 2019b). Some of these associations are supported by findings at molecular level at different stages of the disease pathways (Ambrosone et al, 2015;Daraei et al, 2019;Day et al, 2017;Mansoori et al, 2018;Warren Andersen et al, 2014). Furthermore, early age of menarche creates a gap between biological and social maturity, with being biologically adult but socially and legally minor (Gluckman & Hanson, 2006) possibly leading to early sexual debut, potential sexual abuse, alcohol use, and psychosocial difficulties (Deardorff et al, 2005;Golub et al, 2008).…”

A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer

“…This locus has been previously associated with breast (43–45), prostate (18, 46), and mucinous ovarian cancer risk (24). Of the associated SNPs at RAD51B , two were previously reported in the literature, rs10483813 and rs17828907 (18, 43–45, 47, 48). No associations were detected for mucinous ovarian cancer at this locus, but this may be due to the relatively small number of mucinous ovarian cancer cases included in this analysis (n = 306).…”

Pregnancy-associated breast cancer: the risky status quo and new concepts of predictive medicine

“…The long period of time between the first menstrual bleeding (menarche) and the first full-term pregnancy is a well-known risk factor for the BC carcinogenesis [69,70]. The prolongation of this time period leads to the substantial increase in hormonal stress resulting in the development of precancerous sites in the breast tissue and thus the more pronounced predisposition to BC later in life [2].…”